Interstitial cystitis is sterile cystitis that occurs primarily in women and is a disease exhibiting symptoms such as severe pain and urinary frequency, urinary urgency, nocturia, and a sense of suprapubic pressure or pain when the bladder is filled, which is alleviated after urination (Expert Opinion on Invest Drug, 10: p.521).
The abacterial prostatitis is sterile prostatitis that is diagnosed on the basis of white blood cell counts and quantitative determination of bacteria in urine specimens according to the disease classification of Drach, et al. (1978), and is thought as a variant of condition of interstitial cystitis (Expert Opinion on Invest Drug, 10: p.521).
Hypersensitive disorder of the lower urinary tract as referred to herein means the state of exhibiting a pain by hypersensitivity in any one of the bladder or urethra and occurs even in the absence of infectious diseases in the urinary tract or apparent pathological changes in the bladder wall and urethra. During the infusion period of cytometrogram, there is no increase in the intravesical pressure (lower than 15 cm H2O); nonetheless, the physiological bladder volume is small, and these finding are characteristics for this disorder (Diagnostic Criteria of the Hypersensitive Disorders by N J R George in Sensory Disorders of the Bladder and Urethra, edited by N J R George and J A Gosling, Springer-Verlag, Berilin, 1986, pp.17-29).
With respect to drugs to treat interstitial cystitis, the intravesical administration of dimethyl sulfoxide (DMSO) is approved by Food and Drug Administration in the United States, and its mechanism of action is considered to be desensitization of capsaicin-sensitive sensory nerves (Expert Opinion on Invest Drug, 10: p.521 and J. Urol., 158: pp.1989-1995). Also, it is reported that the intravesical instillation of capsaicin or resiniferatoxin, that is with the same pharmacological action, improves pain or other symptoms of interstitial cystitis in clinical testing (J. Urol., 157, Suppl: p.254 (1997) and J. Urol., 163, Suppl: p.60 (2000)).
In addition, it is suggested that resiniferatoxin is effective against symptoms, such as urinary urgency and bladder pain, due to hypersensitive disorder of the lower urinary tract that is not accompanied with interstitial cystitis nor the typical pathological change (J. Urol., 164: pp.676-679 (2000)). Accordingly, it is considered that drugs having a depressant action on capsaicin-sensitive sensory nerves are effective for improving pain and symptoms in interstitial cystitis, hypersensitive disorder of the lower urinary tract, and/or abacterial prostatitis.
Thus, for the purpose of creating a novel therapeutic drug capable of improving pain and symptoms in interstitial cystitis, hypersensitive disorder of the lower urinary tract, and abacterial prostatitis, the present inventors made extensive and intensive investigations on a compound having a depressant action on capsaicin-sensitive sensory nerves.